E2F/DP complexes play a pivotal role in the regulation of the G1/S transition in animals. This family contains the transcription factor E2F and its dimerisation partners TDP1 and TDP2, which stimulate E2F-dependent transcription. E2F binds to DNA as a homodimer or as a heterodimer in association with TDP1/2, the heterodimer having increased binding efficiency. The crystal structure of an E2F4-DP2-DNA complex shows that the DNA-binding domains (PF02319) of the E2F and DP proteins both have a fold related to the winged-helix DNA-binding motif. Recognition of the central c/gGCGCg/c sequence of the consensus DNA-binding site is symmetric, and amino acids that contact these bases are conserved among all known E2F and DP proteins (Zheng et al., 1995).
Among the six E2F transcription factors (E2Fa, E2Fb, E2Fc, EDL1/E2Fe, EDL2/E2Fd, EDL3/E2Ff) in Arabidopsis, both E2Fa and E2Fb are transcriptional activators, while E2Fc acts as a repressor of the cell cycle. The other three E2F proteins, repressing E2F-regulated reporter genes, are also functional repressors (Xie et al., 2022). Overexpression of both E2Fa and its partner DIMERIZATION PARTNER (DPa) in Arabidopsis can stimulate cell proliferation and induce extra rounds of DNA replication, which result in cell endoreduplication (De Veylder et al., 2022). AtDPa and AtE2Fa are predominantly produced in actively dividing cells with highest transcript levels in early S phase cells. In Arabidopsis, AtNAC1 maintains root meristem size and therefore root growth through directly repressing the transcription of E2Fa (Xie et al., 2022).
In maize expression of Retinoblastoma-related 3 (RBR3) is controlled by RBR1 through the activity of E2F/DP and RBR3 is the maize equivalent of mammalian p107 (Sabelli et al 2005). The main RBR protein domains and interactions with E2Fs are conserved in all eukaryotes and not only regulate the G1/S transition but also the G2/M transition, as part of DREAM complexes (Desvoyes et al., 2020). There are approximately 20 members of the E2F/DP family in maize.
Last updated June 2023 by John Gray
Zheng N, Fraenkel E, Pabo CO, Pavletich NP. Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP. Genes Dev. 1999 Mar 15;13(6):666-74. doi: 10.1101/gad.13.6.666. PMID: 10090723; PMCID: PMC316551.
Xie C, Ding Z. NAC1 Maintains Root Meristem Activity by Repressing the Transcription of E2Fa in Arabidopsis. Int J Mol Sci. 2022 Oct 14;23(20):12258. doi: 10.3390/ijms232012258. PMID: 36293114; PMCID: PMC9603599.
De Veylder L, Beeckman T, Beemster GT, de Almeida Engler J, Ormenese S, Maes S, Naudts M, Van Der Schueren E, Jacqmard A, Engler G, Inzé D. Control of proliferation, endoreduplication and differentiation by the Arabidopsis E2Fa-DPa transcription factor. EMBO J. 2002 Mar 15;21(6):1360-8. doi: 10.1093/emboj/21.6.1360. PMID: 11889041; PMCID: PMC125359.
Sabelli PA, Dante RA, Leiva-Neto JT, Jung R, Gordon-Kamm WJ, Larkins BA. RBR3, a member of the retinoblastoma-related family from maize, is regulated by the RBR1/E2F pathway. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13005-12. doi: 10.1073/pnas.0506160102. Epub 2005 Sep 1. PMID: 16141340; PMCID: PMC1201608.
Desvoyes B, Gutierrez C. Roles of plant retinoblastoma protein: cell cycle and beyond. EMBO J. 2020 Oct 1;39(19):e105802. doi: 10.15252/embj.2020105802. Epub 2020 Aug 31. PMID: 32865261; PMCID: PMC7527812.